Rates of cardiovascular morbidity and mortality are between 10 and 30-fold higher among hemodialysis patients as compared to the general population, and exceed that which is expected on the basis of traditional risk factors. Intra-dialytic hypotension is highly prevalent and a potentially modifiable factor that may contribute to the burden of cardiovascular disease by creating supply-demand mismatch in the coronary circulation, interrupting end organ perfusion and compromising adequate removal of fluid and toxins during dialysis. This study will examine the association between the frequency and severity of intra-dialytic hypotension and all-cause mortality, and cardiovascular mortality and morbidity. All-cause mortality will be examined in a large, national cohort of prevalent dialysis patients to ensure broad generalizability. Cardiovascular endpoints will be examined using data from the Hemodialysis (HEMO) Study because of the rigorous and standardized process by which attribution of death and hospitalization events were adjudicated. In addition, the study will examine the effects of serum magnesium level on the frequency and severity of intra- dialytic hypotension, as one potential means of therapeutic intervention. Upon successful completion, this study will provide evidence as to whether cardiovascular health and survival among hemodialysis patients might be improved via targeted reductions in intra-dialytic hypotension. In addition, the data will offer insights as to potential means by which intra-dialytic hypotension might be manipulated. These findings hold great and immediate implications for clinical care of this highly vulnerable population, and will also provide fodder for future investigation. PUBLIC HEALTH RELEVANCE: Over 350,000 patients with end-stage renal failure are on chronic hemodialysis in the United States alone, and rates of cardiovascular morbidity and mortality are between 10 and 30-fold higher among hemodialysis patients as compared to the general population, exceeding that which is expected on the basis of traditional risk factors. Intra-dialytic hypotension occurs in between 15 and 25% of all dialysis treatments and is a potentially modifiable factor that may contribute to mortality and the burden of cardiovascular disease, with serum magnesium disequilibrium as a potentially cause.